Trichodysplasia spinulosa polyomavirus

Trichodysplasia spinulosa polyomavirus (TSPyV) is a small non-enveloped DNA virus that, like the other human polyomaviruses, is acquired in childhood and carried harmlessly for life by most people. It is clinically important for a single rare disease that bears its name: trichodysplasia spinulosa, a disfiguring follicular skin condition seen almost exclusively in immunosuppressed patients, above all organ transplant recipients. In that disease the virus replicates productively in the cells of the hair follicle and drives them to overgrow, producing the characteristic spiny keratin projections on the face and the loss of the eyebrows and eyelashes. The condition is distressing but not dangerous, and it tends to improve when immune function is restored. TSPyV is one of the alphapolyomaviruses, the same genus as Merkel cell polyomavirus, but its disease results from productive viral replication rather than from the integration and transformation that drive Merkel cell carcinoma.

Discovery and historical significance

Trichodysplasia spinulosa polyomavirus was identified in 2010 by van der Meijden and colleagues, who amplified viral DNA by rolling-circle amplification directly from the keratin spicules plucked from the face of a heart transplant recipient with trichodysplasia spinulosa. The disease had been described before the virus was known, and the discovery established its cause. It was the eighth human polyomavirus to be described and is one of the small number with a defined disease association, alongside JC, BK and Merkel cell polyomaviruses.

Classification, structure, and genome

The virus belongs to the family Polyomaviridae, genus Alphapolyomavirus, with the current International Committee on Taxonomy of Viruses species name Alphapolyomavirus octihominis (formerly Human polyomavirus 8). It is a typical polyomavirus: a non-enveloped icosahedral particle about 40 to 45 nanometres across, built from 72 pentamers of VP1, with a circular double-stranded DNA genome of about 5,000 base pairs encoding the early large T and small t antigens and the late capsid proteins VP1, VP2 and VP3.

Replication cycle

After silent childhood infection the virus persists, like the other human polyomaviruses, at a low level under immune control. In trichodysplasia spinulosa it replicates productively in the cells of the hair follicle: the genome is delivered to the nucleus, large T antigen drives the cell into S phase, viral DNA replicates, the late genes are expressed and complete virions are assembled. This productive infection, generating abundant viral particles in the affected follicles, is the opposite of the abortive, integrated state of Merkel cell polyomavirus in its tumour, where the virus cannot replicate and only transforms.

Pathogenesis

The disease is a direct consequence of productive viral replication in the inner root sheath cells of the hair follicle, which occurs only when immunosuppression removes the T-cell control that normally keeps the virus silent. The large T antigen drives these follicular cells to proliferate and to differentiate abnormally, over-expanding the follicle and producing the dense keratin spicule that protrudes from the skin surface. The process is confined to the follicles and does not transform cells or threaten life; it is a proliferative rather than an oncogenic outcome of polyomavirus infection.

Epidemiology

The virus is common: adult seroprevalence is around 70 per cent, rising from a low level in young children, so primary infection is widespread and silent. Trichodysplasia spinulosa, by contrast, is very rare, with only a small number of reported cases, almost all in immunosuppressed people, predominantly solid organ transplant recipients and occasionally patients with leukaemia.

Natural history

Primary infection in childhood is asymptomatic and is followed by lifelong persistence. In the immunocompetent host the virus never causes disease. Trichodysplasia spinulosa develops only during significant immunosuppression and tends to regress when immune function is restored, so its course follows the state of the host’s immunity rather than any fixed progression.

Clinical presentations and complications

The only disease is trichodysplasia spinulosa. It presents as a follicular eruption of small papules each bearing a fine keratin spicule, concentrated on the central face, the nose, cheeks and ears, often with thickening of the affected skin. Loss of the eyebrows and eyelashes is characteristic, and extensive disease can give a coarse, leonine facial appearance. The condition is disfiguring and cosmetically distressing but is not painful or life-threatening and does not become malignant.

Diagnosis

Diagnosis rests on the clinical appearance in an immunosuppressed patient, confirmed by skin biopsy. The histology shows greatly distended hair follicles with an expanded population of inner root sheath cells containing abundant eosinophilic trichohyalin granules. The virus can be confirmed by PCR for TSPyV DNA, by immunohistochemistry, or by visualising polyomavirus particles on electron microscopy of the spicules.

Management

There is no specific licensed therapy, and management follows the principle common to the polyomaviruses: restore immune control. Where the underlying condition allows, immunosuppression is reduced, which alone can lead to improvement. Topical antiviral treatment, in particular cidofovir applied to the skin, and topical retinoids have been used with reported benefit, and oral valganciclovir has been tried. These are principles rather than established regimens, given how few cases exist.

Prevention and public health

Vaccination

There is no vaccine against the virus, and because it is common and acquired silently in childhood there is no way to prevent infection. Prevention of disease amounts to careful management of immunosuppression and prompt recognition of the characteristic eruption in at-risk patients.

South African context

Trichodysplasia spinulosa is very rare and has no specific South African data or surveillance. Its relevance locally is confined to the transplant and haematology-oncology services that care for immunosuppressed patients, where the distinctive facial eruption should be recognised and confirmed histologically, and managed by adjusting immunosuppression in conjunction with the transplant team.